Mutation

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Mutation

A mutation is the alteration in the composition in deoxyribonucleic acid (DNA) . Mutations that are inherited can change the character of a species . Living organisms rely upon change as a means of adapting to new environments or conditions. Change is a crucial survival mechanism. Evolution hinges on the appearance and inheritance of mutations. Mutations are the source of genetic variation in humans and other life forms, and are a feature of all life, from microorganisms to humans.

Mutation involves a change in one or more of the constituents of deoxyribonucleic acid (DNA). Because DNA provides the blueprint of an organism's operation and appearance, a genetic change in DNA will be evident as a change in an organism's appearance, behavior , or health. Mutated offspring can be quite different in appearance from their parents. For example, a mutation in the gene that determines the production of skin pigment can produce the fair skin, white hair, and eye difficulties that are characteristics of albinism . Dwarfs are an example of a mutation that affects growth hormones .

Mutations can be harmful or can be beneficial. If harmful, the mutation will be selected out over time . The beneficial mutations will be retained. The change in a species over time is the underpinning of evolution.

Mutational errors in DNA

For much of our recorded history, the sudden appearance of an altered person, plant , animal , or other living creature was mysterious and feared, and was typically attributed to some divine intervention. Beginning with the observations of Gregor Mendel on the effects of breeding peas of differing appearance, the genetic basis of mutation became recognized and accepted. A greater understanding of the mechanics of mutation came from the experiments conducted by Thomas H. Morgan in 1910 with fruit fly mutations, and George W. Beadle and Edward L. Tatum in the 1940s on bread mold mutations. The publication of the structure and composition of DNA by Francis Crick and James Watson in 1953 paved the way for the understanding of the molecular basis of mutation.

In eukaryotic organisms such as humans every cell contains DNA arranged on threadlike structures. The structures are called chromosomes. Within the chromosomes lie the regions of DNA called genes that contain the information for proteins . Human beings carry about 30,000 genes on their chromosomes. If the DNA of a particular gene is altered, that gene will become changed. If the change is minor, the mutation may not even be apparent or may be irrelevant to the three dimensional structure and the function of the protein that is produced. But, even an alteration at a single site in a gene can produce drastic alteration of the protein. The protein may not function correctly or may not function at all.

Just one missing or abnormal protein can have an enormous effect on the entire body. For example, the multiple effects that are associated with an albino are the result of one missing protein.

DNA is made up of subunits known as nucleotide bases. There are four kinds of bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The arrangement and different combinations of the bases determines the genetic information, analogous to the arrangement of letters to form words. Mistakes in the genetic code occur when any of these nucleotide bases are absent or duplicated or misplaced. Mutation can be thought of as a kind of molecular typographical error.

As an example, a stretch of DNA could have the following arrangement of bases: ATCTTTGGT. A mutation could occur that produces repeats of some of the bases, as in the italicized region that follows: ATCATCATCTTTGGT. The added bases disrupt the arrangement of the bases, and so disrupt the information contained in the base sequence. An example is Huntington's disease . The presence of two copies of a mutated gene (one from each parent) causes the progressive degeneration of the nervous system and leads to death of the afflicted person in their 40s or 50s. The Huntington's disease mutation is caused by a repeating sequence of three bases in the gene.

Other mutations include the presence of an incorrect base at a certain point, and a missing base (a deletion mutation).

An example of a disease that results from a deletion mutation is cystic fibrosis . The presence of mutated genes in which three thymine bases are absent produces cells in the lungs that are defective in the transport of molecules such as sodium . A result is the accumulation of mucus in the lungs. Bacteria readily colonize the mucus and become resistant to treatments intended to kill them. As well, the host's immune response to the invading bacteria causes progressive damage to lung tissue . The infections and impaired lung function can cause a premature death.

Mutational errors can extend to include more than just one base of a chromosome . Humans normally have 23 pairs of chromosomes. But mutations can produce a fetus that has an extra copy or copies of a chromosome. The unique physical appearance and retarded mental faculties associated with Down syndrome arise when three copies of chromosome 21 are present. Another type of chromosomal mutation occurs when portions of two adjacent chromosomes swap places with each other. Such a translocation mutation between chromosomes 9 and 22 lead to a certain type of leukemia .

Mutations that occur in the egg or sperm cells of a eukaryote are called germinal mutations. These mutations can be inherited by subsequent generations. In contrast, somatic mutations, which occur in cells other than sex cells, cannot be inherited.

Causes of mutation

Mutations also arise naturally during the manufacture of DNA. Thus, the opportunity for error exists every time a cell replicates. Even so, DNA is correctly made almost always. Predictably, cells that divide numerous times are more at risk for errors than cells that divide less frequently. For example, the egg cells are present in a female at birth and never undergo division, while sperm cells in males are constantly being produced. A theory proposes that the cause of birth defects including a type of dwarfism, Marfan syndrome , and myositis ossificans are typically the result of a defective gene contributed by a mutated sperm.

Developing embryos and fetuses are especially at risk for mutation. Their cells divide very rapidly and become increasingly specialized for specific tasks. Pregnant women must be careful to avoid x rays , almost all medication, and even the extreme temperatures of hot tubs and saunas.

Mutations can occur after birth as well. For example, evidence is mounting that environmental influences can trigger genetic changes. A compound that is responsible is termed a mutagen . The known association between some types of cancer and smoking, for example, may result from a mutation in lung cells that overrides the natural controls to cell growth and division. The rampant growth that can occur produces a cancer.

Mutation and evolution

Mutation conjures up images of a sudden and dramatic alteration in appearance, behavior, or some other characteristic of living organisms. Indeed, this aspect was the basis of the term mutation when it was coined in 1901 by Dutch botanist Hugo De Vries. But, the term mutation also refers to the inheritance of an altered gene, even through multiple generations.

Every human genetic trait is subject to mutation. Indeed, some mutations—like hairless skin—must have occurred long ago because they are shared by all humans. Other traits occur only in certain populations of people. Cystic fibrosis, for instance, is most common in people of northern European descent. Sickle cell anemia , a serious blood disease, occurs frequently in people of African and Mediterranean ancestry. Tay-Sachs disease , a fatal disorder, is found primarily in Jews with eastern European ancestors. This suggests that the first person in whom such a mutation occurred came from that particular ethnic group. It may be that not enough time has lapsed, evolutionarily, to allow the mutation to spread to the wider population. Or, it can also be true that a mutation confers a selective advantage on a certain group of people. An example of the latter point is sickle cell anemia , which, in native Africans, can be protective against malaria .

Over millions of years, advantageous mutations have allowed life to develop and diversify from primitive cells into the multitude of species on Earth today, including Homo sapiens. Indeed, the appearance of a mutation, the "testing" of that mutation, and the subsequent inheritance or noninheritance of the mutation is the driving force of evolution. If DNA always replicated perfectly and with no change, every life form from bacteria to humans would have remained unchanged for the entire time of their existence on Earth. Since the planet has and continues to experience change, the inability to adapt to the changes would doom a species to extinction .

Mutations have been exploited by man for commercial purposes. Animal and plant breeders use mutations to produce new or improved species of crops and livestock . Careful breeding in this manner has spawned all the different species of dogs and horses we know today. It has resulted in crops that are resistant to drought or insecta and whose yield is improved. Controlled mutation and breeding has produced goldfish, yellow roses, and Concord grapes .

The processes that generate mutations are collectively termed mutagenesis . In the laboratory, mutagenesis can be accomplished in a controlled and precise manner. This genetic technique is called insertional mutagenesis. It is used to selectively disable genes, in order to find out what functional significance the gene product has to the cell. The ability of microbiologists to introduce controlled and precise mutations in the genetic material of bacteria and viruses can increase the understanding of the operation of the organisms, and of the mechanisms they use to cause disease. Other uses of the technique include the study of gene expression and the study of how a protein's three-dimensional structure influences its function.

Resources

books

Lee, Thomas F. The Human Genome Project. New York: Plenum Press, 1991.

Pollack, Robert. Signs of Life: The Language and Meanings ofDNA. Boston: Houghton Mifflin Company, 1994.

Wilcox, Frank H. DNA: The Thread of Life. Minneapolis: Lerner Publications Company, 1988.

periodicals

Angier, Natalie. "Genetic Mutations Tied to Father in Most Cases." New York Times (May 17, 1994): B9.

Angier, Natalie. "Researchers Trace the Primary Cause of Cystic Fibrosis to the Stone Age." New York Times (June 1, 1994): A13.

Blakeslee, Sandra. "Genes Tell Story of Why Some Get Cancer While Others Don't." New York Times (May 17, 1994): B6.

Nickerson, M.L., Weirich, G., Zbar, B., L.S. Schmidt. "Signature-based Analysis of MET Proto-oncogene Mutations Using DHPLC. Human Mutation 16 (2000): 68-76.

Brian Hoyle

KEY TERMS

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Genome: —The complete set of genes an organism carries.
Germinal mutation: —A mutation in the germ cells (sperm or egg cells). This mutation can be passed on to succeeding generations.
Nucleotide base: —One of the four chemical subunits of DNA: adenine, cytosine, guanine, and thymine.
Somatic mutation: —A mutation in the body cells. This mutation cannot be passed on.
Translocation: —A genetic term referring to a situation during cell division in which a piece of one chromosome breaks off and sticks to another chromosome.